Recent evidence indicates that cytotoxic thymus-derived lymphocytes (T cells) express two orders of specificty: for neoantigen, whether virus, hapten or tumor-specific transplantation antigen (TSTA), and for major histocompatibility complex (MHC) gene products. This raises central questions concerning both the role of te MHC in cell-surface monitoring, and the nature of the T cell receptor repertoire. The present proposal is concerned with using thoracic duct lymphocyte (TDL) cannulation techniques to examine such questions. Protocols for differential selection of TDL populations will be exploited o obtain lymphocytes depleted of, or enriched for, reactivity to particular determinants (Neoantigen or alloantigen). This will facilitate function. Furthermore, the availability of T cells specifically depleted of alloreactive potential should allow assessment of possible interactions between subsets of neoantigen-specific T cells associated with different regions of the MHC. Mechanisms underlying immune response (Ir) gene function may thus be approached. Concurrent studies will made of the recirculation characteristics of cytotoxic (other than alloreactive) T cells and their precursors, and their contribution to immunological surveillance will be assessed. The question of whether mouse T cell responses can be used to define human TSTA's will be analyzed using man-mouse hybrid cells as immunogens, together with negative-selection procedures to remove unwanted clones of lymphocytes.